Liapis H, Crouch E C, Grosso L E, Kitazawa S, Wick M R
Department of Pathology, Washington University Medical Center, St. Louis, MO 63110.
Am J Pathol. 1993 Oct;143(4):1169-78.
Parathyroidlike peptide (PLP), or parathyroid hormone-related protein, is a protein of uncertain biological function that is structurally homologous to parathyroid hormone. Immunohistochemical studies have identified aminoterminal epitopes of PLP in breast carcinomas, but not in normal breast. In the present studies, immunohistochemistry and in situ hybridization were performed to evaluate further expression of PLP in normal, proliferative, and neoplastic breast tissues. Using a polyclonal antibody that recognizes epitopes within the middle and carboxyl-terminal domains of PLP, immunoreactive protein was detected within the cytoplasm of lobular and ductal epithelial cells in all normal and fibrocystic breast tissues from 74 patients. The intensity of cytoplasmic staining was increased in association with lactation, adenosis, and simple or atypical ductal hyperplasia and decreased in atrophic lobules. Cytoplasmic reactivity was also observed in 69% (56 of 81) of breast adenocarcinomas. Expression of immunoreactive PLP was inversely correlated with tumor stage and extent of nodal involvement at the time of diagnosis. However, there was no significant correlation with tumor grade, patient age, or hormone receptor status. In situ hybridization studies confirmed the epithelial expression of PLP messenger RNA in PLP-positive normal and neoplastic breast tissue. Interestingly, tumor-associated calcifications were identified in 43% of PLP-positive carcinomas, but in only 12% of PLP-negative carcinomas (P < 0.007). Our results suggest that PLP plays some role in the normal differentiated function of mammary epithelial cells and are consistent with the hypothesis that expression of this protein influences local calcium metabolism.
甲状旁腺素样肽（PLP），即甲状旁腺激素相关蛋白，是一种生物学功能不明的蛋白质，其结构与甲状旁腺激素同源。免疫组织化学研究已在乳腺癌中鉴定出PLP的氨基末端表位，但在正常乳腺中未发现。在本研究中，采用免疫组织化学和原位杂交技术进一步评估PLP在正常、增生性和肿瘤性乳腺组织中的表达。使用一种识别PLP中间和羧基末端结构域内表位的多克隆抗体，在74例患者所有正常和纤维囊性乳腺组织的小叶和导管上皮细胞胞质内检测到免疫反应性蛋白。胞质染色强度在哺乳期、腺病、单纯性或非典型导管增生时增加，在萎缩性小叶中降低。在81例乳腺腺癌中有69%（56例）也观察到胞质反应性。免疫反应性PLP的表达与诊断时的肿瘤分期和淋巴结受累程度呈负相关。然而，与肿瘤分级、患者年龄或激素受体状态无显著相关性。原位杂交研究证实了PLP阳性的正常和肿瘤性乳腺组织中PLP信使核糖核酸的上皮表达。有趣的是，在43%的PLP阳性癌中发现了肿瘤相关钙化，而在PLP阴性癌中仅为12%（P<0.007）。我们的结果表明，PLP在乳腺上皮细胞的正常分化功能中起一定作用，并且与该蛋白的表达影响局部钙代谢的假说一致。
